Screening Crucial Genes For Glucose Metabolism In Rheumatoid Arthritis

Objectives:Studies have indicated that glucose metabolism plays an important role in the pathogenesis of rheumatoid arthritis (RA). This study aimed to screen the novel genes affecting glucose metabolism in RA and investigated their pathogenic mechanism.Methods:Collagen-induced arthritis (CIA) was prepared with rats and their synovial tissues were analyzed with Rat Glucose Metabolism RT2 ProfilerTM PCR Array to screen those genes with special expressions inglucose metabolism.Real-time PCR, western blotting and ELISAwas used to confirm the result in the synovial tissues and blood of human RA. RA synovial tissues were cultured and synovial fibroblast cells (RASF) were treated with siRNA to suppress expressions of the target genes. CCK-8 cell proliferation assay and 2-compartment transwell system were performed to examine cell proliferation and cell migration of the treated RASF. ELISA was also used to examine cytokine productions in supernatant of the cultured RASF.Results:The PCR array detected the up-regulation of ENO1, HK2 and PGK1 and the down-regulation of PCK1 and PDK4 in synovial tissues of CIA rats. Real-time PCR and western blotting detected the increased expression of ENO1 and PGK1 in RA synovial tissues. ELISA detected a high level of PGK1 in the blood of RA patients. Decreased cell proliferation and cell migration capabilities were significantly detected in RASF following treatment of anti-PGK1 siRNA. IL-1β and IFN-γ levels rather than TNF-α and IL-1α levels were significantly declined insupernatants of the treated RASF.Conclusions:PGK1, a glycolytic enzyme catalyzing the conversion of 3-phosphoglycerate into 2-phosphoglycerate, has increased expression in CIA and RA synovial tissues and blood of patients with RA, which is involved in abnormal cell proliferation and cell migration as well as abnormal IL-1β and IFN-γ production in RA.